Osteosarcoma (OS) is the most common primary malignant bone tumor that more commonly occurs in children and adolescents. The most commonly used treatment for OS is surgery combined with chemotherapy, but the treatment outcomes are typically unsatisfactory. High rates of metastasis and post-treatment recurrence rates are major challenges in the treatment of OS. This underlines the need for studying the in-depth characterization of the pathogenetic mechanisms of OS and development of more effective therapeutic modalities. Previous studies have demonstrated the important role of the bone microenvironment and the regulation of signaling pathways in the occurrence and development of OS. In this review, we discussed the available evidence pertaining to the mechanisms of OS development and identified therapeutic targets for OS. We also summarized the available treatment modalities for OS and identified future priorities for therapeutics research.
Child ; Adolescent ; Humans ; Bone Neoplasms/drug therapy* ; Signal Transduction ; Bone and Bones/metabolism* ; Treatment Outcome ; Osteosarcoma/drug therapy* ; Tumor Microenvironment

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg^-1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
Mice ; Male ; Female ; Animals ; Familial Hypophosphatemic Rickets/metabolism* ; Bone and Bones/metabolism* ; Tooth/metabolism* ; Periodontal Ligament/metabolism*

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg^-1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3-7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.
Humans ; Male ; Mice ; Animals ; Familial Hypophosphatemic Rickets/pathology* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/metabolism* ; Bone and Bones/metabolism* ; Phosphates/therapeutic use*

Tissue regeneration is an important engineering method for the treatment of oral soft and hard tissue defects.Growth factors,as one of the three elements of tissue regeneration,are a necessary condition for tissue regeneration.Concentrated growth factor(CGF)is a new generation of blood extract prepared by changing the centrifugal speed on the basis of the preparation of platelet-rich plasma(PRP)and platelet-rich fibrin(PRF).It contains abundant growth factors and a fibrin matrix with a three-dimensional network structure,being capable of activating angiogenesis and promoting tissue regeneration and healing.CGF has been widely used in the repair and regeneration of oral soft and hard tissues.This paper introduces the preparation and composition of CGF and reviews the application of CGF in oral implantation and the regeneration of oral bone tissue,periodontal tissue,and dental pulp tissue.
Platelet-Rich Plasma/metabolism* ; Platelet-Rich Fibrin ; Cell Proliferation ; Bone and Bones ; Intercellular Signaling Peptides and Proteins/metabolism* ; Bone Regeneration

Collagen, which widely exists in skin, bone, muscle and other tissues, is a major structural protein in mammalian extracellular matrix. It participates in cell proliferation, differentiation, migration and signal transmission, plays an important role in tissue support and repair and exerts a protective effect. Collagen is widely used in tissue engineering, clinical medicine, food industry, packaging materials, cosmetics and medical beauty due to its good biological characteristics. This paper reviews the biological characteristics of collagen and its application in bioengineering research and development in recent years. Finally, we prospect the future application of collagen as a biomimetic material.
Animals ; Collagen/analysis* ; Tissue Engineering/methods* ; Extracellular Matrix/metabolism* ; Biomimetic Materials/chemistry* ; Bone and Bones ; Tissue Scaffolds ; Mammals/metabolism*

OBJECTIVES: To study the level of serum vitamin K₂ (VitK₂) and its association with bone metabolism markers osteocalcin (OC), type I procollagen amino-terminal peptide (PINP), and type I collagen carboxy-terminal peptide (CTX) in children. METHODS: A prospective analysis was performed on 1 732 children who underwent routine physical examination from October 2020 to October 2021. The serum levels of VitK₂ and 25-hydroxy vitamin D [25(OH)D] were measured. According to age, they were divided into four groups: <1 year, 1-3 years group, >3-6 years group, and >6-14 years. A total of 309 children with 25(OH)D≥50 nmol/L were screened out, and serum levels of OC, PINP, and CTX were measured to investigate the correlation of the serum levels of OC, PINP, and CTX with serum VitK₂ levels in different age groups. RESULTS: The prevalence rate of serum VitK₂ deficiency was 52.31% (906/1 732). The VitK₂ deficiency group had higher prevalence rates of overweight/obesity and growth pain (≥3 years of age) than the normal VitK₂ group (P<0.05). There were differences in the prevalence rate of serum VitK₂ deficiency (P<0.0083) and the serum level of VitK₂ (P<0.05) between the 1-3 years group and the >6-14 years group. The <1 year group had a higher serum level of CTX and a lower serum level of PINP than the >3-6 years group and the >6-14 years group (P<0.05). The <1 year group had a lower serum level of OC than the >6-14 years group (P<0.05). Serum VitK₂ level was positively correlated with OC level (r_s=0.347, P<0.01), and CTX level was negatively correlated with PINP level (r_s=-0.317, P<0.01). CONCLUSIONS Serum VitK₂ deficiency may be associated with overweight/obesity. Serum VitK₂ may affect the level of OC and even bone health.
Child ; Humans ; Infant ; Biomarkers/metabolism* ; Collagen Type I/metabolism* ; Obesity/complications* ; Osteocalcin/metabolism* ; Overweight/complications* ; Peptide Fragments/metabolism* ; Peptides/metabolism* ; Procollagen/metabolism* ; Vitamin K/blood* ; Child, Preschool ; Adolescent ; Bone and Bones/metabolism*

The maintenance of bone homeostasis is critical for bone health. It is vulnerable to cause bone loss, even severely osteoporosis when the balance between bone formation and absorption is interrupted. Growing evidence has shown that energy metabolism disorders, such as abnormal glucose metabolism, irregular amino acid metabolism, and aberrant lipid metabolism, can damage bone homeostasis, causing or exacerbating bone mass loss and osteoporosis-related fractures. Here, we summarize the studies of energy metabolism in osteoblasts and osteoclasts and provide a better appreciation of how energy metabolism, especially glucose metabolism maintains bone homeostasis. With this knowledge, new avenues will be unraveled to understand and cue bone-related diseases such as osteoporosis.
Bone and Bones ; Energy Metabolism ; Osteoblasts ; Osteoclasts ; Osteogenesis

In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.
Anti-Bacterial Agents/administration & dosage* ; Bone and Bones/metabolism* ; Cellular Microenvironment ; Humans ; Immune System/immunology* ; Lymphocyte Subsets/immunology* ; Osteitis/microbiology* ; Osteoblasts/physiology* ; Osteoclasts/physiology* ; Staphylococcal Infections

Homoeostasis depends on the close connection and intimate molecular exchange between extracellular, intracellular and intercellular networks. Intercellular communication is largely mediated by gap junctions (GJs), a type of specialized membrane contact composed of variable number of channels that enable direct communication between cells by allowing small molecules to pass directly into the cytoplasm of neighbouring cells. Although considerable evidence indicates that gap junctions contribute to the functions of many organs, such as the bone, intestine, kidney, heart, brain and nerve, less is known about their role in oral development and disease. In this review, the current progress in understanding the background of connexins and the functions of gap junctions in oral development and diseases is discussed. The homoeostasis of tooth and periodontal tissues, normal tooth and maxillofacial development, saliva secretion and the integrity of the oral mucosa depend on the proper function of gap junctions. Knowledge of this pattern of cell-cell communication is required for a better understanding of oral diseases. With the ever-increasing understanding of connexins in oral diseases, therapeutic strategies could be developed to target these membrane channels in various oral diseases and maxillofacial dysplasia.
Bone and Bones ; Cell Communication ; Connexins ; metabolism ; physiology ; Gap Junctions ; metabolism ; pathology ; Homeostasis ; physiology ; Humans ; Mouth Diseases ; Phosphorylation

OBJECTIVE: To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts. METHODS: Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; =6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of β-catenin and RANKL protein in the cells were analyzed. RESULTS: The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice ( < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice ( < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of β-catenin and increased the expression of RANKL as compared with TPTD treatment alone. CONCLUSIONS Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.
Animals ; Bone Density ; Bone Density Conservation Agents ; administration & dosage ; pharmacology ; Bone Resorption ; drug therapy ; Bone and Bones ; drug effects ; metabolism ; Female ; Growth Plate ; drug effects ; Mice ; Mice, Inbred C57BL ; Osteoclasts ; drug effects ; Ovariectomy ; RANK Ligand ; metabolism ; Teriparatide ; administration & dosage ; pharmacology ; beta Catenin ; metabolism